The aim of the proposed work is to investigate some pathogenic mechanisms of nephritis and renal allograft rejection. Three hundred renal tissue specimens from patients with glomerulonephritis or interstitial nephritis will be studied every year by light, electron and immunofluorescence microscopy; the sera of patients as well as the eluates of kidneys obtained after nephrectomy from Buffalo and Denver Transplantation Units will be tested for presence of circulating antigen-antibody complexes or for presence of antibodies to GBM or TBM. The possible transformation of immune complex into antibasement membrane nephritis (and vice-versa) will be investigated in man and in experimental animals. The role of cell-mediated mechanisms in interstitial nephritis will be studied in man, or in thymectomized or bursectomized chickens injected with homologous kidney suspension, with the aid of techniques which identify B and T lymphocytes. The ultrastructure of immune complex interstitial pneumonitis and the role of the septal cells will be studied together with the turnover of radio-labeled antigen in the lung. Similar studies will be performed in the spleen of rabbits with splenitis produced by circulating antigen-antibody complexes. Systematic studies of the lung and the spleen will be also performed in patients with SLE. Cr31-labeled albumin will be used to trace the permeability of gastrointestinal tract in rabbits with "membranous intestinal disease" produced by deposition of circulating antigen-antibody complexes. The studies concerning the morphological basis of glomerular permeability will be extended to rabbits with acute serum sickness. The immunopathologic changes of renal allografts will be correlated with those of the patient's own kidneys; the possible role of autoantibodies or of circulating transplantation antigen-antibody complexes will be studied in rats transplanted against a weak histocompatibility barrier.